Lifestyle patterns, such as consuming a low-fat dietary pattern and regular physical activity, are associated with reduced risk of cardiovascular disease (CVD) and improvement in CVD risk factors. It is less clear how these lifestyle behaviors are associated with emerging risk factors thought to play an important role in development of CVD, such as inflammation. Cross-sectional studies indicate that vigorous physical activity is associated with lower inflammatory markers, particularly C-reactive protein (CRP). A limited number of interventions suggest that regular physical activity may reduce CRP levels, but previous studies have had small sample sizes and no control groups. In contrast, only a few cross-sectional studies have assessed associations among a low-fat diet and CRP, and there is a suggestion that dietary intakes low in fat are associated with higher CRP levels. No interventions have evaluated the effects of a low-fat diet on CRP. Thus, major questions about lifestyle patterns on CRP have not been answered: Can regular physical activity reduce CRP? Does a low-fat diet not benefit CRP? What happens if these lifestyle factors are combined? These questions are critical to answer in order to design optimal lifestyle interventions to reduce risk of CVD in high-risk populations. The data set from the Diet and Exercise for Elevated Risk (DEER) trial, a randomized, controlled trial can answer these important questions. 197 men and 180 postmenopausal women with unfavorable lipoprotein levels were randomized to a 1-year trial of a (1) low-fat diet;(2) regular physical activity;(3) diet and physical activity;(4) control. Stored specimens are available to measure plasma CRP levels. This research will determine the effects of diet and physical activity, alone and in combination, on CRP relative to the control group, and explore combinations of dietary patterns and physical activity to reduce CRP levels in high-risk individuals. This application responds to PA 06-181 by testing the feasibility of lifestyle interventions on CRP in high-risk individuals to explore a new scientific area. Public Health Relevance: Recent evidence has emerged that inflammation is a key factor in the development of coronary heart disease. There are currently no recommendations for lifestyle changes that can reduce markers of inflammation. This study will use an existing data set to test whether a low-fat diet, increased physical activity, each alone or combined, can reduce markers of inflammation. These results can help determine what the optimal lifestyle changes are necessary to reduce inflammation, with the ultimate goal of reducing risk for coronary heart disease.